Many of the differential effects of sigma-like compounds may be explained by the heterogeneity of sigma binding sites. Our studies have established filtration binding assay condition using [3H]SKF10047 to label a sigma-1 site and [3H]DTG to label a sigma-2 site. These sites have distinct and different pharmacology as well as separate brain distributions as revealed by receptor autoradiography. Using these assay conditions we tried to replicate a recent report of reduced sigma binding in the brains of genetically dystonic rats. We wanted to test the hypothesis that sigma, especially sigma-2 sites played a role in this motor disorder. We were unable to confirm the changes in the brains of these dystonic animals and believe they were an artifact of the small number of experiments performed by the other laboratory investigating these animals. We are now investigating the distribution of these two sigma receptor subtypes in the postmortem brains of schizophrenics to determine the relative contribution of each of these sites to the decrease in sigma binding reported by us in the temporal lobe of schizophrenics.